Antigen-induced breakdown of membrane phospholipids in basophilic RBL-2H3 cells, appeared to be mediated by a G protein and a tyrosine kinase, and possibly regulated by a phosphatase. Other stimulants, for example, adenosine analogs or carbachol, in RBL-2H3 cells transfected with the gene for the muscarinic ml receptors, operated exclusively through G- proteins to activate phospholipase C and other phospholipases. The ensuing events, however, such as mobilization of intra- and extra- cellular Ca2+, activation of protein kinase C and exocytosis appeared to be identical for all stimulants. In particular, all stimulants recruited Ca2+ from the same intracellular pool of Ca2+ and utilized the same Ca2+- influx mechanism. Studies with washed permeabilized RBL-2H3 cells have revealed that exocytosis was dependent on both an elevated [Ca2+]i and activation of protein kinase C but that at early stages of the response a G protein-mediated event may replace the requirement for elevated [Ca2+]i. Distal to these events, the action of a p40. Mitogen Activated Protein (MAP) kinase was apparent with all secretagogues and the secretory responses were blocked by inhibitors of tyrosine phosphatase(s). Thus late steps in exocytosis may be regulated by MAP kinase and tyrosine phosphatase(s). The discovery of a novel 100 kDa monomeric G protein in RBL cells, and the partial cloning of the gene for this protein, have revealed unique features that warrant further studies.